Process for acylation



Patented Aug. 15, 1944 PROCESS FOR ACYLATION Virgil n Hansley, Niagara Falls, N. in, aslignor to E. I. du Pont de Nemours a Company, Wilmington, Del., a corporation of Delaware I No Drawing. Original application April 19, 1941,

Divided and this application August 20, 1943, Serial No. 499,381

Serial No. 389,359.

6 Claims.

This invention relates to a process for the acylation of organic compounds and particularly to a process for the acylation of certain secondary alcohols which utilizes vinyl esters as acylating agents.

This application is a division of my copending application, Serial No. 389,359, filed April 19, 1941; now Patent No. 2,342,612.

The prior art discloses no method for utilizing vinyl esters as acylating agents in the acylation of the substituted secondary alcohols with which the present invention is concerned.

One of the objects of this invention is to provide a new and improved method for the acylation of certain secondary alcohols. Another object is to provide a practical and economical method for the acylation of these secondary alcohols by which good yields of the desired ester may be obtained. A further object is to provide a method for the acylation of certain secondary alcohols which is simple to operate and which may be carried out at comparatively low temperatures in easily obtainable equipment. These and other objects will be apparent from the ensuing description of my invention.

The above objects are attained in accordance with my invention by reacting a vinyl ester with certain secondary alcohols in the presence of a tertiary amine which is sufilciently alkaline to maintain a pH greater than 7.0 in the reaction medium.

I have found that when a vinyl ester, for example, vinyl acetate, is added to certain secondary alcohols in the presence of such tertiary amines, the reaction is smooth, rapid, and substantially complete and the desired ester is readily obtained in good yield.

The tertiary amines which I have found effective as catalysts for'the reaction between the secondary alcohols and vinyl esters are those tertiary amines which are sufliciently alkaline to produce an alkaline reaction medium. Illustrative of the tertiary amines which are satisfactory as catalysts in the process of my invention are triethylamine and tributyl amine. I have discovered that when such tertiary amines are added to a mixture containing a vinyl ester and certain secondary alcohols, in amounts suflicient to maintain a pH greater than 7.0, good yields of the desired ester are obtained. When the pH of the reaction medium is maintained considerably above 7.0, for instance, 8.0 to 9.0 or higher, the reaction may be very rapid and in some cases violent. At a pH of 7.0 or less little or no reaction occurs and I have discovered that it is essential that sumcient tertiary amine be utilized to maintain the pH of the reaction medium somewhat above 7.0 in order to obtain appreciable quantities of the desired ester by the process of my invention. I prefer to maintain a pH of 7.5 to 9.0 since I have found that in general the best results are obtained within this range.

However, the pH of the reaction medium may be maintained above 9.0 by means of the tertiary amine catalyst with satisfactory results, and in certain cases, for example when utilizing secondary alcohols which react comparatively slowly with the vinyl ester such procedure may be desirable.

The rate of reaction may be controlled by the rate of addition of tertiary amine catalyst or one of the reactants and cooling or heating the reaction mixture. While th reaction with some secondary alcohols is rapid and strongly exothermic, with others the reaction is slower and in some instances a longer time or hig er temperature or a combination of these conditions may be utilized to insure complete reaction. For instance, in

' some cases it has proven desirable to permit the reaction mixture to stand at room temperature for a few days or to reflux the mixture in order to insure complete reaction.

The particular tertiary amine which is most suitable for use in carrying out a specified acylation according to my invention may depend upon the boiling points of the materials involved in the reaction. Generally, it is preferable to utilize a tertiary amine which may easily be separated from the reaction mixture by distillation in order to simplify recovery of the desired product in pure form.

It is generally preferable that the tertiary amine catalyst used in the process of my invention be substantially anhydrous since the presence of water in the reaction may result in a loss of the desired product due to hydrolysis.

The process of my invention may be carried out at any desired temperature compatible with the particular reactants used and the product obtained. Generally, I have found it desirable to operate my process at about room temperature and in some cases as high as C. to C.

In some instances it may be preferable to reflux wherein R2 is selected from the group consisting of halo-methyl, cyano, cyano-methyl. aldomethyl, hydroxy-methyl, alkoxy-methyl, aryloxy-methyl, acyloxy-methyl, ester, and 2-oxy-2 cyano-ethyl radicals and R1 is selected from the group consisting of alkyl, aryl, hydro-aromatic, hydroxy-alkyl, and the radicals identical with R2.

. pressure.

boiling point l5-'l6 C. at 20 mm. pressure. The yield was 56% of the theoretical, based on the amount of methyl lactate used.

Example 2 Eighty-six grams of vinyl acetate were added in small portions to a mixture of 71 grams lactonitrile and 5 grams of'triethylamine. The vigorous reaction was controlled by the use of an ice bath. After all the vinyl acetate had been added, the mixture was distilled at reduced One hundred grams of lactonitrile acetate were obtained, boiling point 73 C. at 19 Throughout the claims the substituent radicals of the secondary alcoholic compounds which are operable in the process of my invention are defined as follows: halo-methyl designates the radicals CH:X in which X may be chlorine, bromine, or iodine; the cyano radical, -CN; cyano methyl, CH2CN; hydroxy methyl, CH2OH; ester, -CO0Y and acyloxy-methyl,

' CH2OOCY, in which Y is an alkyl or aryl radical; aldo-methyl, -CH2CHO; alkoxy or arm- ,oxy methyl, --CH2OY in which Y is an alkyl or aryl radical; 2-oxy 2-eyano ethyl,

n CHs3-CN in which Z is an oxy radical; and hydro-aromatic is a cyclo-paraflln radical such as cyclohexyl.

Illustrative of the secondary alcohols which I have observed to aoylate readily in accordance with the process of my invention are methyl lactate, aldol, glycerol, diacetin, aldol cyanhydrin, lactonitrile, glycerol alpha-gamma-dichlorohydrin. Compounds such as aceto-acetic ester and beta-cyano beta-acetoxy-cthyl methyl carbinol are also operative in the process of my invention. I

The following procedure illustrates a satisfactory method of carrying out the process of my invention. The secondary alcohol to be acylated is placed in a suitable reaction vessel. For carrying out the process on a small scale a threenecked flask equipped with a stirrer and inlet for vinyl ester may conveniently be used. The reaction flask is immersed in a batharranged for heating or cooling and sufilcient tertiary amine is added to the compound to be acylated to maintain an alkaline reaction medium. The vinyl ester is added gradually to the contents of the flask while the reaction mixture is agitated.

The rate of addition of vinyl ester and the rate,

Example 1 Ninety grams of vinyl acetate were added to a mixture of 104 grams of methyl lactate and 19 grams of triethylamine. The mixture was allowed to stand at room temperature for five days. Upon vacuum distillation 82 grams 0! methyl alpha-acetoxy propionate .were obtained,

mm. pressure. The yield was 88.5% of the theoretical, based on th amount of lactonitrile used.

Example 3 Ninety grams of vinyl acetate were added to a mixture of 1'76 grams of diacetin and 15 grams of triethylamine. The mixture was allowed to stand at room temperature for five days, and

after neutralization with phosphoric acid, the sample was distilled at 5 mm. pressure. The portion of distillate which came over at 128-129 C. was washed once with ml. of water, then re-dlstilled at reduced pressure. One hundred thirty-six grams of triacetln were obtained, a yield of 62%, based on the quantity of diacetin used. The boiling point was 154 C. at 22 mm. pressure.

Example 4 Eighty-six grams of vinyl acetate were added in small portions to a mixture of 129 grams of glycerol alpha-gamma-dichlorohydrin and 24 grams of triethylamine. Within half an hour after mixing, a fairly vigorous exothermic reaction took place. The mixture was then refiuxed for fifteen minutes. After being cooled and neutralized with phosphoric acid, the sample was distilled at 20 mm. pressure, The fraction boiling above 80 C. was re-distilled at 10mm and grams of the acetate of glycerol alphagamma-dichloro-hydrin were obtained, an 88% yield, based on the amount of dichlorohydrin used. The boiling point of the esterwas 77 C. at 10 mm. pressure.

Example 5 Example 6 Twenty-six and seven-tenths grams (26.7) of vinyl propionate were added in small portions to a mixture of 14.2 grams of lactonitrile and 1.0 grams of triethylamine. A fairly vigorous exothermic reaction occurred at once. After neutralization with phosphoric acid, the sample was vacuum distilled, and 22 grams of lactonitrile propionate, boiling at 57-58" C. at 5 mm. pressure,.

were obtained. The yield was 87% of the theo-. retical, based on the quantity of lactonitrile em ployed.

Example 7 Ten grams of tri-n-butylamine were added dropwise to a mixture of 190 grams of lactonitril and 260 grams of vinyl acetate. A vigorous reaction occurred, which was controlled by the use of an ice bath. The mixture was then neutralized with phosphoric acid. Upon distilling at 20 mm. pressure, 283 grams of lactonitrile acetate were obtained, a 94% yield, on the basis of the quantity of lactonitrile used.

In general, I prefer to use approximately equimolecular proportions of secondary alcohol and vinyl ster since the reaction is substantially complete and an excess of either reactant is not required. However, in some instances it may be found desirable to use an excess of one of the reactants. For example, such an excess may be utilized as a solvent for the reaction mixture.

Many modifications of my invention may be made without departing from the scope thereof; My process may be carried out as a batch or as a continuous process. Moreover, the reaction may be carried out in the presence of solvents inert with respect to the reactants and catalyst employed. Also the products may be recovered by means other than distillation. For example, the acetaldehyde formed may be removed by adding an agent which will react with the 'acetaldehyde to form a compound capable of being removed by mechanical means. Vinyl esters other than vinyl acetate, for instance vinyl formate, vinyl propionate or vinyl butyrate may be utilized as the acylating agent. Many other modifications will be apparent to those skilled in the art without departing from the scope of this invention, the essential feature of which comprises a process for the acylation of certain secondary alcohols by reacting said alcohols with a vinyl ester in the presence of a tertiary amine which is sufliciently alkalin to maintain a pH greater than 7.0 in the reaction medium and maintaining the pH of the reaction mixture above 7.0 by means of said tertiary amine.

The process of my invention is useful in the preparation of a wide variety of esters which may be used as solvents or for the synthesis of other compounds.

The process of my invention possesses many advantages which will be apparent to those skilled in the art. Th process is simple and easily operated on any desired scale, high yields of the desired esters are obtained and the product is easily isolated in pure form. Furthermore, the use of a tertiary amine as a catalyst avoids the necessity for corrosion resistant equipment such as is required by a process which utilizes acidic materials. A further important advantag resides in the fact that the process of my invention may be operated efllciently at comparatively low temperatures thus avoiding undesirable side reactions and consequent loss in yield which occur at high temperatures. The process of my invention is valuable for the preparation of esters of certain secondary alcoholic compounds since no previous method which utilizes vinyl esters for the acylation of these compounds is known.

I claim:

l. The process for the acylation of methyl lactate which comprises reacting a vinyl ester with methyl lactate in the presence of a tertiary amine of suitabl alkalinity and maintaining the pH of the reaction mixture above 7.0 by means of said tertiary amine.

2. The process which comprises reacting vinyl formate with methyl lactate in the presence of a tertiary amin of suitable alkalinity and maintaining the pH of the reaction mixture above 7.0 by means of said tertiary amine.

3. The process which comprises reacting vinyl butyrate with methyl lactate in the presence of a tertiary amine of suitable alkalinity and maintaining the pH of the reaction mixture above 7.0 by means of said tertiary amine.

4. The process for the acetylation of methyl lactate which comprises reacting vinyl acetate with methyl lactate in the presence of triethylamine and maintaining the pH of the reaction mixture above 7.0 by means of said triethylamine.

5. The process for the acylation of methyl lactate which comprises reacting a vinyl ester with methyl lactate in the presence of tributylamine and maintaining the pH of the reaction mixture above 7.0 by means of said tributylamine.

6. The process for the acetylation of methyl lactate which comprises reacting vinyl acetate with methyl lactate in the presence of tributylamine and maintaining the pH of the reaction mixture above 7.0 by means of said tributylamine.

VIRGIL L. HANSLEY. 

